DALLAS, June 8  Blood levels of two metals  lead and cadmium  may increase the risk of peripheral artery disease  even at levels currently considered safe, according to research published in today's rapid access issue of Circulation: Journal of the American Heart Association.

The general public can be exposed to lead and cadmium through cigarette smoke, in ambient air near industrial and combustion sources, in certain foods and sometimes in drinking water.
Peripheral artery disease or PAD affects 8 to 12 million Americans, according to the American Heart Association. It is a condition similar to coronary artery disease and carotid artery disease. In PAD, fatty deposits build up in artery walls and reduce blood circulation, mainly in arteries to the legs and feet. In its early stages a common symptom is cramping or fatigue in the legs and buttocks during activity. Such cramping subsides when the person stands still.

In a study of 2,125 adults, those with the highest blood concentrations of lead or cadmium were almost three times more likely to develop PAD than those with the lowest levels of the two metals. Yet the highest levels were well within what is currently considered safe levels, said senior author Eliseo Guallar, M.D., DrPH, an assistant professor of epidemiology at the Johns Hopkins University Bloomberg School of Public Health in Baltimore.

Both metals are well-known toxins, Guallar said, but the levels found in the subjects "are well below the radar screen of current regulations." The new finding suggests that epidemiologists as well as basic scientists "need to think more carefully about this association and do more experiments with cadmium and lead at lower doses to determine what exposures [to the metals] might be problematic in terms of risk for cardiovascular disease."

The study includes data from adults aged 40 or older who participated in the 1999-2000 National Health and Nutrition Examination Survey (NHANES). The participants were separated into four groups based on the level of the metals in their blood.

There was a significant association between cadmium blood levels and PAD. People
with the highest cadmium levels were 2.82 times more likely to develop PAD than people with the lowest levels.

The trend in the association between PAD and blood lead from the lowest quartile to the highest quartile was significant. The odds ratio for developing PAD was 2.88 for those with the highest blood lead levels compared to those with the lowest levels of lead in their blood.

PAD was associated with blood lead concentrations that were 13.8 percent higher on average than in subjects without PAD, Guallar said. Likewise, the cadmium levels were about 16.1 percent higher in persons with PAD than in those without PAD.

Guallar said that as research has uncovered more information about the true dangers of lead, regulators steadily lowered the threshold for so-called "safe" levels. "A decade ago, what was considered a safe level for lead was much higher than it is today," he said.

Peripheral artery disease is strongly associated with smoking, which is confirmed in the present study, Guallar said. In this study the odds of PAD for current smokers compared to people who never smoked was 4.13. The odds were reduced to 3.38 after adjustment for blood lead and to 1.84 after adjustment for blood cadmium. This led Guallar to theorize that the cadmium contained in cigarette smoke may damage the lining of blood vessels and be a major factor in smoking-associated PAD.

The researchers identified PAD by measuring blood pressure in the right arm  the brachial artery  and in both ankles to obtain the ankle-brachial index. This index is calculated by dividing the mean systolic pressure in each ankle by the mean systolic pressure in the arm. PAD was defined as an ankle-brachial index (ABI) of less than 0.90 in at least one leg. Additionally, blood tests were done to determine cadmium and lead levels.

Overall, the average blood level of lead was 0.10 micromoles per liter (ìmol/L) while the average for cadmium was 4.3 nanamoles per liter (nmol/L). The Occupational Safety and Health Administration (OSHA) safety standard for lead in whole blood is 1.93 umol/L or lower. For cadmium the OSHA acceptable level is 44.5 nmol/L.

In general, subjects who were older, less educated and smokers had higher levels of both lead and cadmium. Concentrations of both metals were highest in smokers, but smoking was more strongly associated with cadmium, Guallar said.

Researchers suggest the findings need to be confirmed in prospective studies and mechanistic studies of low-level lead and cadmium exposure.

"We don't need any more reasons to argue that smoking is bad, but it is important to know what are the mechanisms of the problems associated with smoking. We need to know if there is something about cigarette smoke that makes it more specific to PAD than other vascular diseases," he said.